Biology subjects

Goldfarb, A. M.

Publications and source records attributed to Goldfarb, A. M..

2 recordsLinked to original sources

bioRxiv2026

Functional diversification across yeast lineages of the nucleus-vacuole junction forming protein Nvj1

Nucleus-vacuole junctions (NVJs) in Saccharomyces cerevisiae serve as an inter-organellar hub for multiple cell processes, including lipid transport and biosynthesis, an intra-nuclear quality control mechanism, and piecemeal microautophagy of the nucleus. NVJs are formed by complexes between Vac8 in the vacuole membrane and Nvj1 in the nuclear envelope. Nvj1 also links the inner and outer nuclear membranes across the perinuclear lumen. Orthologs of Nvj1 had previously only been found in yeasts of the order Saccharomycetales, raising the possibility that NVJs are restricted to this clade. Using homology and synteny, we discovered scores of novel Nvj1 orthologs across 200 million years of evolution within the subphylum Saccharomycotina. Not all orthologs mediate NVJ formation when expressed in S. cerevisiae, and some lack a sequence motif necessary for this function. Furthermore, the sequence motif required for binding the oxysterol binding protein Osh1 and an associated novel sequence motif, both found only in the order Saccharomycetales, were independently lost in three different lineages. This collection suggests specific opportunities to explore evolutionary and functional adaptations of Nvj1s in ecologically and physiologically diverse yeasts.

cell biology↗

bioRxiv2024

Tetrameric TRF2 forms t-loop to protect telomeres from ATM signaling and cNHEJ

Telomeres often occur in the t-loop structure, formed through the base-pairing of the 3 telomeric overhang is base-paired with more internal telomeric DNA. T-loops are proposed to avert ATM kinase signaling and classical non-homologous end joining (cNHEJ) by sequestering the telomere end. The shelterin subunit TRF2 is required for t-loop formation but how it generates t-loops is not known and the t-loop model for telomere protection remains untested. We show that TRF2 binds telomeric DNA as a tetramer using two dimerization domains and that tetramerization is critical for telomere protection. Furthermore, TRF1, the TRF2 paralog that binds DNA as a dimer and does not form t-loops, gained the ability to form t-loops in vivo upon its tetramerization through the addition of a second dimerization domain. We propose that TRF2 tetramers loop telomeric DNA, resulting in torsional stress and opening of the helix, which is a requirement for t-loop formation. Importantly, t-loops formed by tetrameric TRF1 were sufficient to avert ATM signaling and blocked most cNHEJ at telomeres, demonstrating that t-loops per se protect telomeres from these threats.

cell biology↗